APPLICANT'S ABSTRACT: Alcohol abuse and alcoholism are often associated with concurrent nicotine use and abuse. The central research goal of this new small grant application is to determine the influence of nicotine on the motivational (rewarding and aversive) effects of ethanol. Three behavioral indices of motivational effects of ethanol (place conditioning, taste conditioning, drinking) will be used to characterize the effects of ethanol, nicotine and ethanol with nicotine.These responses will be studied in mice after acute nicotine exposure in order to determine the initial influence of nicotine on ethanol's rewarding and aversive effects. Additionally, these responses will be studied in mice after repeated nicotine exposures in order to characterize the role of nicotine tolerance and/or sensitization on the motivational response to ethanol. The place conditioning procedure will provide an estimate of ethanol rewarding effects (ethanol-induced conditioning place preference). Ethanol-induced place preference will be determined in the drug free state and after nicotine exposure. These two testing conditioning will allow for the determination of the importance of the nicotine drug state on the expression of conditioned reward to ethanol. This procedure will also allow determination of the influence of nicotine on ethanol-induced locomotor activation during the conditioning process. Ethanol-induced locomotor activation is taken to reflect the euphoriant properties of ethanol. The taste conditioning procedure will provide an assessment of ethanol's aversive effects (ethanol-induced taste aversion) both alone and in combination with nicotine. This procedure will allow determination of the development of aversion to ethanol paired flavor cues over a series of conditioning trials. Ethanol drinking will be determined in mice after repeated exposure to nicotine. This experiment will characterize the effect of nicotine on oral ethanol reinforcement. These experiments offer the first systematic characterization of the interaction between nicotine and ethanol on motivational responses to ethanol. Using well developed behavioral procedures we will be able to determine the rewarding and aversive efficacy of each drug separately and together.These experiments will provide important new information on the effects of ethanol and nicotine on motivational processes which are often seen as critical for the development of alcohol abuse and alcoholism.